Photo-BQCA: Positive Allosteric Modulators Enabling Optical Control of the M1 Receptor

The field of G protein-coupled receptor (GPCR) research has greatly benefited from the spatiotemporal resolution provided by light controllable, i.e., photoswitchable ligands. Most of the developed tools have targeted the Rhodopsin-like family (Class A), the largest family of GPCRs. However, to date...

Descripción completa

Detalles Bibliográficos
Autores: Gerwe, Hubert, Schaller, Eva, Sortino, Rosalba, Opar, Ekin, Martinez Tambella, Joaquin, Bermudez, Marcel, Lane, J Robert, Gorostiza Langa, Pablo Ignacio, Decker, Michael
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/217335
Acceso en línea:https://hdl.handle.net/2445/217335
Access Level:acceso abierto
Palabra clave:Fotofarmacologia
Enzims al·lostèrics
Photopharmacology
Allosteric enzymes
Descripción
Sumario:The field of G protein-coupled receptor (GPCR) research has greatly benefited from the spatiotemporal resolution provided by light controllable, i.e., photoswitchable ligands. Most of the developed tools have targeted the Rhodopsin-like family (Class A), the largest family of GPCRs. However, to date, all such Class A photoswitchable ligands were designed to act at the orthosteric binding site of these receptors. Herein, we report the development of the first photoswitchable allosteric modulators of Class A GPCRs, designed to target the M-1 muscarinic acetylcholine receptor. The presented benzyl quinolone carboxylic acid (BQCA) derivatives, Photo-BQCisA and Photo-BQCtrAns, exhibit complementary photopharmacological behavior and allow reversible control of the receptor using light as an external stimulus. This makes them valuable tools to further investigate M-1 receptor signaling and a proof of concept for photoswitchable allosteric modulators at Class A receptors.